Urinary Biomarkers in Interstitial Cystitis and Bladder Pain Syndrome: A Narrative Review of Differential Diagnosis and Treatment Monitoring.

Abstract

Introduction and hypothesis: The objective was to narratively synthesize clinical studies of urinary biomarkers in interstitial cystitis/bladder pain syndrome (IC/BPS) and evaluate their utility for differential diagnosis versus overactive bladder (OAB), pre-cystoscopy biomarker enrichment for Hunner-lesion IC (HIC), and monitoring treatment response.

Methods: We conducted a narrative review of MEDLINE/PubMed records available through June 2026, no start-date restriction, and screened reference lists of the articles included. Studies assessing urinary cytokines and chemokines, neurotrophins and growth factors, or oxidative-stress markers in IC/BPS against healthy or symptomatic comparators and across bladder-directed treatment cohorts were eligible. Thirty-five articles met the inclusion criteria; heterogeneity in biomarkers, assay platforms, normalization strategies, comparators, and outcomes precluded meta-analysis.

Results: Among the 35 articles included, the strongest single-marker performance for IC/BPS versus controls was urinary TNF-α (area under the curve [AUC] 0.92; sensitivity 99.0%; specificity 92.6%). Against overactive bladder, VEGF, CXCL10, and IL-8 gave AUCs of 0.87, 0.86, and 0.81, and a pilot algorithm used MIP-1β as an initial screen (sensitivity 92.2%) with eotaxin, CXCL10, and RANTES as confirmatory markers for IC/BPS. For pre-cystoscopic Hunner-lesion enrichment, urinary CXCL10 separated Hunner-type from non-Hunner-type disease (AUC 0.78, sensitivity 46.1%, specificity 93.7%, positive predictive value 97.7%); CXCL10 plus NGF reached an AUC of 0.81. Combining biomarkers with simple clinical variables outperformed biomarkers alone: 8-OHdG, TNF-α, and a bladder-pain visual analog scale score reached an AUC of 0.997 with 96% accuracy, and in an external validation the urinary biomarker cluster alone reached an AUC of 0.65, rising to 0.89 once age, bladder pain score, and the IC Problem Index were added, although those clinical variables alone performed comparably (AUC 0.89); thus, incremental value over routine clinical assessment was not demonstrated. Higher urinary CXCL10 correlated with O'Leary-Sant symptom and problem scores (both p = 0.02). In treatment-monitoring studies biomarker shifts accompanied rather than preceded clinical improvement: after sacral neuromodulation urinary MCP-1 fell from 448.3 to 176.9 pg/ml and sIL-1RA from 633.8 to 149.9 pg/ml at 24 weeks; after four monthly platelet-rich plasma injections, NGF, MMP-13, and VEGF fell whereas PDGF-AB rose; and extracorporeal shock wave therapy produced only transient 4-week changes, with none remaining at 12 weeks.

Conclusions: Current urinary biomarkers can assist, but not replace, standard clinical assessment and selective cystoscopy. At present, their clearest near-term roles are in research and selected specialist settings, including adjunctive differentiation of IC/BPS from overactive bladder or other lower urinary tract dysfunctions, pre-cystoscopic enrichment for Hunner-lesion disease, and pharmacodynamic monitoring in trials. Routine stand-alone implementation is not yet justified because thresholds, pre-analytics, assay platforms, and external validation remain inconsistent, although external validation of combined biomarker-plus-clinical models has now begun.